Discovery of potential asthma targets based on the clinical efficacy of Traditional Chinese Medicine formulas.

ETHNOPHARMACOLOGICAL RELEVANCE: Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments. AIM OF THE STUDY: Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy. MATERIALS AND METHODS: A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated. RESULTS: The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10-2 mM) and ginkgolide A (1 × 10-5 mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 µg/kg) and ginkgolide A (205 µg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6). CONCLUSION: Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy.

[Response of forest bird communities to forest gap in winter in southwestern China].

Although forest gap ecology is an important field of study, research remains limited. By plot setting and point counted observation, the response of birds to forest gaps in winter as well as bird distribution patterns in forest gaps and intact canopies were studied in a north tropical monsoon forest of southwestern China from November 2011 to February 2012 in the Fangcheng Golden Camellia National Nature Reserve, Guangxi. The regression equation of bird species diversity to habitat factor was Y1=0.611+0.002 X13+0.043 X2+0.002 X5-0.003 X8+0.006 X10+0.008 X1 and the regression equation of bird species dominance index to habitat factor was Y3=0.533+0.001 X13+0.019 X2+0.002 X3-0.017 X4+0.002 X1. There were 45 bird species (2 orders and 13 families) recorded in the forest gap, accounting for 84.9% of all birds (n=45), with an average of 9.6 species (range: 2-22). Thirty-nine bird species (5 orders and 14 families) were recorded in non-gap areas, accounting for 73.6% of all birds (n=39), with an average of 5.3 species (range: 1-12). These results suggested that gap size, arbor average height (10 m from gap margin), arbor quantity (10 m from gap margin), shrub quantity (10 m from gap margin), herbal average coverage (1 m from gap margin) and bare land ratio were the key forest gap factors that influenced bird diversities. On the whole, bird diversity in the forest gap was greater than in the intact canopy. Spatial distributions in the forest gaps were also observed in the bird community. Most birds foraged in the "middle" and "canopy" layers in the vertical stratification. In addition, "nearly from" and "close from" contained more birds in relation to horizontal stratification. Feeding niche differentiation was suggested as the main reason for these distribution patterns.